Septic shock and severe sepsis represent a major public health problem in the United States, despite the development of increasingly powerful antibiotics and advanced forms of intensive care unit-based support modalities (see, e.g., Shanley, T. et al. Sepsis, 3rd Ed., St. Louis, Mo., Mosby (2006)). Worldwide, septic shock affects millions of adults, killing approximately one in four (see, e.g., Dellinger, R. et al. Crit. Care Med. 36:296-327 (2008)). A recent study suggests that the incidence and the mortality rates of septic shock in adults are increasing in the United States (Dombrovskiy, V. et al. Crit. Care Med. 35:1244-50 (2007)).
Septic shock is also a major problem in the pediatric age group, as there are ˜42,000 cases of pediatric septic shock per year in the United States alone, with a mortality rate of ˜10% (see, e.g., Watson, R. et al. Am. J. Respir. Crit. Care Med. 167:695-701 (2003)). While the pediatric mortality rate is lower than that of adults, it nonetheless translates to more than 4,000 childhood deaths per year and countless years of lost productivity due to death at a young age. While this high number of pediatric deaths per year from septic shock indicates that more children die per year in the United States from septic shock as the primary cause than those children who die from cancer, funding specifically targeted toward pediatric septic shock is substantially lower than that for pediatric cancer.
Reliable stratification of outcome risk is fundamental to effective clinical practice and clinical research (Marshall J. Leukoc. Biol. 83:471-82 (2008)). No reliable and widely accepted outcome risk stratification tool specific for septic shock in pediatric patients has heretofore been developed. Such a tool would be beneficial at several levels, including stratification for interventional clinical trials, better-informed decision making for individual patients, and as a metric for quality improvement efforts.